Lenz Microphthalmia Syndrome

Lenz Microphthalmia Syndrome

Overview

Lenz microphthalmia syndrome is an extremely rare inherited disorder characterized by small eyes (microphthalmos or microphthalmia) and/or droopy eyelids (blepharoptosis), resulting in visual impairment. Rarely, affected infants may exhibit complete absence of the eyes (anophthalmos or anophthalmia). Additional physical anomalies are often associated, including a small head (microcephaly) and/or anomalies of the teeth, ears and/or fingers and/or toes (digits). The range and severity of findings may vary from person to person. Most affected children also exhibit developmental delays and intellectual disability.

Lenz microphthalmia syndrome is caused by pathogenic variants, or changes, in the BCOR gene and is inherited in an X-linked pattern. This condition is fully expressed in males only. However, females who carry a variant BCOR gene may exhibit some symptoms, such as microcephaly, short stature and/or anomalies of the fingers and/or toes

Symptoms

In affected males, the primary physical characteristic associated with Lenz microphthalmia syndrome is small eyes (one eye or both). In most cases, both eyes are affected and the eyes maybe of different size (bilateral, asymmetrical microphthalmos/microphthalmia). The front (anterior), clear portion of the eye through which light passes (cornea) may be small (microcornea). In addition, the colored portion of the eye (iris) may be differently formed with absent tissue (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other parts of the eye, including the ciliary body, choroid and/or optic disc. In many patients, the upper eyelids may droop (blepharoptosis) due to paralysis of muscles that control the eyelids. In rare cases, affected infants may exhibit absence or only rudimentary (vestigial) portions of the eyes (anophthalmos/anophthalmia). Such eye findings may result in varying degrees of visual impairment or, in some people, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.

Affected males may exhibit mild to severe delays in attaining certain developmental milestones (e.g., crawling, sitting independently, walking, etc.) and intellectual disability ranging from mild to severe.

Most infants with Lenz microphthalmia syndrome also exhibit additional physical findings, such as anomalies of the head and facial (craniofacial) area. These usually include a small head (microcephaly) and anomalies of the ears and teeth. In most infants with this disorder, the ears are flexed forward (anteverted), and the ear lobes may be large; however, in some children, the ears may also be small and underdeveloped (hypoplastic). Hearing impairment may be present in some people. The teeth may be widely spaced or abnormally crowded. In addition, the front teeth (incisors) may be absent (dental agenesis or anodontia) or malformed. Some affected males may exhibit incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove or incomplete closure of the upper lip (cleft lip).

Most males with the disorder also have skeletal anomalies. These may include a lateral (sideways) and front-to-back (anterior-posterior) curvature of the spine (kyphoscoliosis), narrow and/or sloping shoulders, underdeveloped collarbones (hypoplastic clavicles) and/or a differently shaped rib cage (thoracic cage).

In addition, infants with Lenz microphthalmia syndrome often exhibit anomalies of the fingers and/or toes (digits). The digits may be bent (clinodactyly), flexed (camptodactyly) and/or joined (syndactyly). In some people, double thumbs may also be present.

Approximately half of affected males may also have abnormalities of the reproductive and urinary (genitourinary) systems. These malformations may include failure of the testes to descend into the scrotum (cryptorchidism), placement of the urinary opening (meatus) on the underside of the penis (hypospadias) and/or underdevelopment (hypoplasia) or absence (agenesis) of a kidney (renal agenesis).

Females who carry a single variant in the gene for Lenz microphthalmia syndrome (heterozygous carriers) may exhibit some of the symptoms associated with the disease. In this situation, the symptoms are typically milder than those associated with the fully expressed disorder in males. Heterozygous females may have anomalies in the fingers and/or toes (digital anomalies), a small head (microcephaly) and/or short stature.

Causes

Lenz microphthalmia syndrome is caused by changes or pathogenic variants in the BCOR gene and is inherited in an X-linked pattern. Some researchers speculate that severe cases of Lenz microphthalmia syndrome may result from deletions of genetic material from two or more adjacent genes (contiguous gene syndrome) located on the X chromosome.

X-linked genetic disorders are conditions caused by a non-working (non-functional) gene on the X chromosome and typically manifest mostly in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not usually display symptoms because females have two X chromosomes and only one carries the non-working gene. However, some carrier females may exhibit some of the symptoms associated with the disorder as mentioned above. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working gene, he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

Affected populations

Approximately 12 affected males with fully expressed Lenz microphthalmia syndrome have been reported in the medical literature.

Diagnosis

The diagnosis of Lenz microphthalmia syndrome may be confirmed at birth, based upon a thorough clinical evaluation, characteristic physical findings and imaging techniques. Ultrasonography studies of the internal structure of the eye may demonstrate that the length from the front to the back of the eye (anteroposterior axis) is smaller than normal, confirming a diagnosis of microphthalmia. In some people, however, it may be difficult to distinguish severe microphthalmia from anophthalmia. Therefore, ultrasound imaging or magnetic resonance imaging (MRI) may sometimes be used to help confirm which condition is present. When MRI scanning is unable to clarify which malformation is present, other diagnostic steps may sometimes be taken to determine whether rudimentary (vestigial) portions of the eyes are present or absent.

Additional diagnostic steps may also be taken to confirm the presence of other physical findings typically associated with Lenz microphthalmia syndrome. Examination with an instrument that visualizes the interior of the eye (ophthalmoscopy) may be used to determine the absence of ocular tissue in the eye (colobomas). Drooping of the upper eyelid (blepharoptosis) may be diagnosed by clinical evaluation, including comparison with the other eyelid (if the anomaly affects only one side) or examination of the infant’s upper gaze. Imaging techniques may confirm the presence of dental, skeletal, genitourinary and/or other anomalies associated with Lenz microphthalmia syndrome.

In some familial cases, Lenz microphthalmia syndrome may be detected before birth (prenatally). For example, ultrasound studies during pregnancy may reveal characteristic findings suggestive of Lenz microphthalmia syndrome in siblings of affected children.

Standard Therapies

Treatment

The treatment of Lenz microphthalmia syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat diseases of the eye (ophthalmologists); dental specialists who diagnose, prevent, and/or correct anomalies of the teeth (orthodontists); specialists who diagnose and treat skeletal anomalies (orthopedists); and/or others may need to work together to ensure a comprehensive approach to treatment.

Specific therapies for the treatment of Lenz microphthalmia syndrome are symptomatic and supportive. In some patients, corrective glasses, contact lenses and/or surgery may be used to help improve vision. Artificial teeth (dentures), dental implants, braces, dental surgery and/or other corrective procedures may be undertaken to correct dental anomalies. Differences in curvature of the spine (kyphoscoliosis) may be treated with a combination of exercises and physical therapy, other supportive techniques, braces, casts, and/or corrective surgery. Surgery may also be performed to correct cleft lip and palate; digital, skeletal and/or genitourinary malformations or other anomalies associated with the disorder.

Early intervention is important to ensure that children with Lenz microphthalmia syndrome reach their potential. Special services that may be beneficial to affected children may include special education and other medical, social and/or vocational services.

Genetic counseling is recommended for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be potentially associated with Lenz microphthalmia syndrome. Other treatment for is symptomatic and supportive.

Type of Doctor Department :Ophthalmologist